PROJECT SUMMARY Obesity is a massive public-health issue in the US. Clinical and epidemiological studies have indicated that increased body weight is related to reduced sleep. In line with this, previous research has shown that sleep deprivation is associated with changes in appetite-regulating hormones. However, the central brain processes that underlie sleep-related changes in food intake are currently unclear. The olfactory system plays an important role in regulating food intake, and animal models indicate that appetite-regulating hormones may alter olfactory processing, suggesting that sleep deprivation may increase neural processing of food stimuli. We propose a feasibility study that aims to provide proof-of-concept data for the hypothesis that sleep deprivation enhances neural processing of food odors (Aim 1). We predict that olfactory cortices are among the first stages in the neural processing hierarchy at which sleep deprivation amplifies signals related to food odors. In a second step, we propose to test whether enhanced processing of food odors is related to alterations in food intake (Aim 2). To test these hypotheses, human subjects will smell odors of food and non- food control odors while undergoing functional magnetic resonance imaging (fMRI), either after a night of normal sleep, or after a night during which they were only allowed to sleep for a maximum of 4 hours. We propose to use pattern-based neuroimaging analysis techniques to determine whether sleep deprivation enhances neural encoding of food odors. To test whether sleep deprivation affects olfactory processing through changes in appetite-regulating hormones, we will measure hormone levels in blood samples collected during fMRI scanning. Finally, to examine whether enhanced olfactory processing affects eating behavior, we will monitor food intake after fMRI scanning in a buffet-style setting. Results from this study should reveal a neuro-hormonal mechanism that mediates the effects of sleep deprivation on eating behavior. Describing this mechanism may ultimately help to develop novel treatment approaches combating obesity.